Loading
NFE2L2 (Nuclear factor erythroid 2-related factor 2) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Lung cancer, Hepatocellular carcinoma, Head and neck squamous cell carcinoma and 5 more.
Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralising reactive electrophiles. In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex. In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, heterodimerisation with one of the small Maf proteins and binding to ARE elements of cytoprotective target genes.
CIViC holds 10 clinical evidence items and 0 assertions across 8 variants, naming Sapanisertib and Platinum Doublet. Open Targets scores its association with cancer at 0.80 (direct and indirect evidence; datatypes clinical 0.14, affected pathway 0.33, literature 1.00, genetic association 0.07, somatic mutation 0.94, animal model 0.53). IntOGen calls it a driver in 18 cohorts (16 activating, 2 loss-of-function), covering Bladder Urothelial Carcinoma, Cervical Squamous Cell Carcinoma, Oesophageal Adenocarcinoma, Hepatocellular Carcinoma, Head and Neck Squamous Cell Carcinoma, Lung Squamous Cell Carcinoma and others.
In plain words · NFE2L2 (Nuclear factor erythroid 2-related factor 2) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Lung cancer, Hepatocellular carcinoma, Head and neck squamous cell carcinoma and 5 more.
NFE2L2 (Nuclear factor erythroid 2-related factor 2) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Lung cancer, Hepatocellular carcinoma, Head and neck squamous cell carcinoma and 5 more.
Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralising reactive electrophiles.
No product in this corpus aims at NFE2L2 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA NFE2L2: RNA low tissue specificity; high antibody staining in 19 normal tissues; highest cancer staining renal cancer (3 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lung cancer (all types), Hepatocellular carcinoma, Head and neck squamous cell carcinoma, Bladder & urothelial cancer, Oesophageal cancer, Endometrial cancer, Cervical cancer and more); Open Targets associates it with 3 specific cancer types at or above 0.5 (hepatocellular carcinoma, squamous cell lung carcinoma, head and neck squamous cell carcinoma). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt Q16236; CIViC gene NFE2L2; IntOGen NFE2L2; Human Protein Atlas NFE2L2 tissue; Open Targets ENSG00000116044 associations
First described 1994. Earliest sequence paper UniProt cites for the protein: Moi et al, Proc. Natl. Acad. Sci. U.S.A, 1994, "Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region". Source.
Sources: HGNC HGNC:7782 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q16236 (protein name, function text, keywords and locations (REST API)); CIViC gene NFE2L2 (10 evidence items, 0 assertions, 8 variants; diseases: Lung Squamous Cell Carcinoma, Lung Non-small Cell Carcinoma, Squamous Cell Carcinoma (GraphQL API, CC0)); Open Targets ENSG00000116044 (association with cancer (MONDO_0004992) 0.80; per-cancer scores at or above 0.5: oesophageal cancer 0.60, hepatocellular carcinoma 0.61, urinary bladder cancer 0.55, ovarian cancer 0.52, endometrial cancer 0.54, head and neck squamous cell carcinoma 0.62 (GraphQL API, CC0)); IntOGen NFE2L2 (driver in 18 cohorts (Act 16, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralising reactive electrophiles. In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex. In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, heterodimerisation with one of the small Maf proteins and binding to ARE elements of cytoprotective target genes. The NFE2L2/NRF2 pathway is also activated in response to selective autophagy: autophagy promotes interaction between KEAP1 and SQSTM1/p62 and subsequent inactivation of the BCR(KEAP1) complex, leading to NFE2L2/NRF2 nuclear accumulation and expression of cytoprotective genes. The NFE2L2/NRF2 pathway is also activated during the unfolded protein response (UPR), contributing to redox homeostasis and cell survival following endoplasmic reticulum stress. May also be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region. Location: Cytoplasm, cytosol; Nucleus (UniProt). Locus 2q31.2 (HGNC).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adipose tissue, Adrenal gland, Appendix, Breast, Bronchus, Colon, Duodenum, Epididymis.
Medium only: breast cancer, colorectal cancer, endometrial cancer, head and neck cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Non-small-cell lung cancer | 12-15% | Hotspot mutation in the KEAP1-binding degrons | cBioPortal: 72 of 484, 14.9%, in lusc_tcga_pan_can_atlas_2018; 27 of 178, 15.2%, in lusc_tcga_pub; 13 of 108, 12.0%, in lusc_cptac_2021; 84 of 1,144, 7.3%, in the combined nsclc_tcga_broad_2016; against 18 of 566, 3.2%, in lung adenocarcinoma. The mutations cluster tightly in the two motifs KEAP1 grips: E79Q (7 records), R34G (6), G31A (5), R34Q (5), D29H (5), R34P (5), D29N (5) and L30F (4) in lusc_tcga_pan_can_atlas_2018. | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
A three-continent cohort from high-incidence countries, and the origin of the idea that a shared frameshift (ELF3) could be a vaccine target in a cancer with few targets. CTNNB1 and STK11 from this list recur in the MSK data.
It separated the prognostic co-mutation, KEAP1, from the predictive one, STK11, in a disease where the two are often quoted together, and it is the reason KEAP1 status is worth reading off a report even though no treatment depends on it.
It explained why squamous lung cancer has no equivalent of an EGFR inhibitor: its commonest alterations are a transcription factor amplicon, a tumour suppressor deletion and an antioxidant switch, none of which is a drug target in the way a mutant kinase is.
Query for this target: (TITLE:"NFE2L2" OR ABSTRACT:"NFE2L2" OR TITLE:"NFE2 like bZIP transcription factor 2" OR ABSTRACT:"NFE2 like bZIP transcription factor 2" OR TITLE:"Nuclear factor erythroid 2-related factor 2" OR ABSTRACT:"Nuclear factor erythroid 2-related factor 2" OR TITLE:"NRF2" OR ABSTRACT:"NRF2" OR TITLE:"NRF-2" OR ABSTRACT:"NRF-2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about NFE2L2, not a curated reading list.
Shares Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate, Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer, KEAP1-NRF2 antioxidant pathway, Comprehensive genomic characterization of squamous cell lung cancers.
Shares Comprehensive genomic characterization of squamous cell lung cancers, Cervical cancer, Bladder & urothelial cancer, IntOGen.
Shares Comprehensive genomic characterization of squamous cell lung cancers, Renal cell carcinoma, CIViC, IntOGen.
Shares Hepatocellular carcinoma (KEGG map), Oesophageal cancer, Hepatocellular carcinoma, IntOGen.
Shares Hepatocellular carcinoma (KEGG map), Bladder & urothelial cancer, CIViC, IntOGen.
Shares Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate, Hepatocellular carcinoma (KEGG map), Endometrial cancer, Renal cell carcinoma.
Shares Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate, Bladder & urothelial cancer, IntOGen, Open Targets Platform.
Shares Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate, Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer, KEAP1-NRF2 antioxidant pathway, Cervical cancer.